Over the past few years, there has been a considerable progress toward the understanding of viral and host genetic factors on HIV transmission and disease progression. However, many gaps still remain. Different subtypes of HIV-1 are distributed unequally worldwide. HIV-1 subtype C is rapidly spreading in southern Africa and Asia and accounts for 50 percent of all HIV-1 infections in the world. Whether a particular subtype of HIV-1 is more transmissible or more pathogenic in certain geographic locations or populations remains an open question. At the same time, although certain host genetic factors such as chemokine receptor gene mutations and differences in HLA alleles have been observed to influence HIV transmission and disease progression in certain populations, whether there exist additional host genetic factors which may also influence HIV transmission and disease progression in under studied populations requires further investigation. The purpose of this study is to characterize the influence of different subtypes of HIV-1 as well as differences in host genetic factors (i.e., genetic polymorphisms) on HIV transmission and disease progression in a cohort of injection drug users from Southern China where emerging HIV-1 infection among IDUs has been documented and epidemiological and behave information are being collected. Also, the distribution and transmission pattern of different HIV-1 subtypes in these IDUs are being studied. In this application, we propose to carry out the following specific aims: (1) To study the influence of viral characteristics including subtype differences, viral load, and phenotype of HIV-1 on HIV transmission and disease progression. (2) To study the influence of host genetic factors on HIV transmission and disease progression. The results of these studies should provide further insight into the mechanism of HIV transmission and pathogenesis.